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This article is part of the supplement: International Meeting on Fibrous Dysplasia/McCune-Albright Syndrome and Cherubism

Open Access Proceedings

The role of SH3BP2 in the pathophysiology of cherubism

Ernst J Reichenberger1*, Michael A Levine2, Bjorn R Olsen3, Maria E Papadaki4 and Steven A Lietman5

Author Affiliations

1 University of Connecticut Health Center, Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, Farmington, CT, USA

2 Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

3 Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA

4 Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA

5 The Departments of Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA

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Orphanet Journal of Rare Diseases 2012, 7(Suppl 1):S5  doi:10.1186/1750-1172-7-S1-S5

Published: 24 May 2012

Abstract

Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans.